Chemogenetic activation of astrocytes promotes remyelination and restores cognitive deficits in visceral hypersensitive rats

Mahadi Hasan; Zhuogui Lei; Mastura Akter; Zafar Iqbal; Faeeqa Usaila; Aruna Surendran Ramkrishnan; Ying Li

doi:10.1016/j.isci.2022.105840

Chemogenetic activation of astrocytes promotes remyelination and restores cognitive deficits in visceral hypersensitive rats

Mahadi Hasan, Zhuogui Lei, Mastura Akter, Zafar Iqbal, Faeeqa Usaila, Aruna Surendran Ramkrishnan, Ying Li^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

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Abstract

Using a well-established chronic visceral hypersensitivity (VH) rat model, we characterized the decrease of myelin basic protein, reduced number of mature oligodendrocytes (OLs), and hypomyelination in the anterior cingulate cortex (ACC). The results of rat gambling test showed impaired decision-making, and the results of electrophysiological studies showed desynchronization in the ACC to basolateral amygdala (BLA) neural circuitry. Astrocytes release various factors that modulate oligodendrocyte progenitor cell proliferation and myelination. Astrocytic Gq-modulation through expression of hM3Dq facilitated oligodendrocyte progenitor cell proliferation and OL differentiation, and enhanced ACC myelination in VH rats. Activating astrocytic Gq rescued impaired decision-making and desynchronization in ACC-BLA. These data indicate that ACC hypomyelination is an important component of impaired decision-making and network desynchronization in VH. Astrocytic Gq activity plays a significant role in oligodendrocyte myelination and decision-making behavior in VH. Insights from these studies have potential for interventions in myelin-related diseases such as chronic pain-associated cognitive disorders.

Original language	English
Article number	105840
Journal	iScience
Volume	26
Issue number	1
Online published	20 Dec 2022
DOIs	https://doi.org/10.1016/j.isci.2022.105840
Publication status	Published - 20 Jan 2023

Funding

We thank Bing He for TEM technical support. This work was supported by the Research Grants Council of Hong Kong (11103721, 11102820, and 11100018), the National Natural Science Foundation of China (NSFC) and RGC Joint Research Scheme (3171101014, N_CityU114/17), HEALTH@InnoHK Program launched by the Innovation and Technology Commission of the Hong Kong SAR, China (CityU 9445909), the Shenzhen-Hong Kong Institute of Brain Science Innovation Open Project Contract (NYKFKT2019012). This work was also supported by City University of Hong Kong Neuroscience Research Infrastructure Grant (9610211), and Centre for Biosystems, Neuroscience, and Nanotechnology Grant (9360148).

Research Keywords

Biological sciences
Cognitive neuroscience
Neuroscience

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This full text is made available under CC-BY-NC-ND 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/

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title = "Chemogenetic activation of astrocytes promotes remyelination and restores cognitive deficits in visceral hypersensitive rats",

abstract = "Using a well-established chronic visceral hypersensitivity (VH) rat model, we characterized the decrease of myelin basic protein, reduced number of mature oligodendrocytes (OLs), and hypomyelination in the anterior cingulate cortex (ACC). The results of rat gambling test showed impaired decision-making, and the results of electrophysiological studies showed desynchronization in the ACC to basolateral amygdala (BLA) neural circuitry. Astrocytes release various factors that modulate oligodendrocyte progenitor cell proliferation and myelination. Astrocytic Gq-modulation through expression of hM3Dq facilitated oligodendrocyte progenitor cell proliferation and OL differentiation, and enhanced ACC myelination in VH rats. Activating astrocytic Gq rescued impaired decision-making and desynchronization in ACC-BLA. These data indicate that ACC hypomyelination is an important component of impaired decision-making and network desynchronization in VH. Astrocytic Gq activity plays a significant role in oligodendrocyte myelination and decision-making behavior in VH. Insights from these studies have potential for interventions in myelin-related diseases such as chronic pain-associated cognitive disorders.",

keywords = "Biological sciences, Cognitive neuroscience, Neuroscience",

author = "Mahadi Hasan and Zhuogui Lei and Mastura Akter and Zafar Iqbal and Faeeqa Usaila and Ramkrishnan, {Aruna Surendran} and Ying Li",

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AU - Hasan, Mahadi

AU - Lei, Zhuogui

AU - Akter, Mastura

AU - Iqbal, Zafar

AU - Usaila, Faeeqa

AU - Ramkrishnan, Aruna Surendran

AU - Li, Ying

PY - 2023/1/20

Y1 - 2023/1/20

N2 - Using a well-established chronic visceral hypersensitivity (VH) rat model, we characterized the decrease of myelin basic protein, reduced number of mature oligodendrocytes (OLs), and hypomyelination in the anterior cingulate cortex (ACC). The results of rat gambling test showed impaired decision-making, and the results of electrophysiological studies showed desynchronization in the ACC to basolateral amygdala (BLA) neural circuitry. Astrocytes release various factors that modulate oligodendrocyte progenitor cell proliferation and myelination. Astrocytic Gq-modulation through expression of hM3Dq facilitated oligodendrocyte progenitor cell proliferation and OL differentiation, and enhanced ACC myelination in VH rats. Activating astrocytic Gq rescued impaired decision-making and desynchronization in ACC-BLA. These data indicate that ACC hypomyelination is an important component of impaired decision-making and network desynchronization in VH. Astrocytic Gq activity plays a significant role in oligodendrocyte myelination and decision-making behavior in VH. Insights from these studies have potential for interventions in myelin-related diseases such as chronic pain-associated cognitive disorders.

AB - Using a well-established chronic visceral hypersensitivity (VH) rat model, we characterized the decrease of myelin basic protein, reduced number of mature oligodendrocytes (OLs), and hypomyelination in the anterior cingulate cortex (ACC). The results of rat gambling test showed impaired decision-making, and the results of electrophysiological studies showed desynchronization in the ACC to basolateral amygdala (BLA) neural circuitry. Astrocytes release various factors that modulate oligodendrocyte progenitor cell proliferation and myelination. Astrocytic Gq-modulation through expression of hM3Dq facilitated oligodendrocyte progenitor cell proliferation and OL differentiation, and enhanced ACC myelination in VH rats. Activating astrocytic Gq rescued impaired decision-making and desynchronization in ACC-BLA. These data indicate that ACC hypomyelination is an important component of impaired decision-making and network desynchronization in VH. Astrocytic Gq activity plays a significant role in oligodendrocyte myelination and decision-making behavior in VH. Insights from these studies have potential for interventions in myelin-related diseases such as chronic pain-associated cognitive disorders.

KW - Biological sciences

KW - Cognitive neuroscience

KW - Neuroscience

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DO - 10.1016/j.isci.2022.105840

M3 - RGC 21 - Publication in refereed journal

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ER -

Chemogenetic activation of astrocytes promotes remyelination and restores cognitive deficits in visceral hypersensitive rats

Abstract

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